rs754474112

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001330723.2(SNX27):c.40C>A(p.Pro14Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,188 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P14S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SNX27
NM_001330723.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.823

Publications

0 publications found

Variant links:

Genes affected

SNX27 (HGNC:20073): (sorting nexin 27) This gene encodes a member of the sorting nexin family, a diverse group of cytoplasmic and membrane-associated proteins involved in endocytosis of plasma membrane receptors and protein trafficking through these compartments. All members of this protein family contain a phosphoinositide binding domain (PX domain). A highly similar protein in mouse is responsible for the specific recruitment of an isoform of serotonin 5-hydroxytryptamine 4 receptor into early endosomes, suggesting the analogous role for the human protein. [provided by RefSeq, Jul 2008]

SNX27 links:

ENSG00000250734 (HGNC:):

ENSG00000250734 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.007129878).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330723.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SNX27	NM_001330723.2	MANE Select	c.40C>A	p.Pro14Thr	missense	Exon 1 of 12	NP_001317652.1	Q96L92-1
SNX27	NM_030918.6		c.40C>A	p.Pro14Thr	missense	Exon 1 of 12	NP_112180.4
SNX27	NM_001437601.1		c.40C>A	p.Pro14Thr	missense	Exon 1 of 11	NP_001424530.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SNX27	ENST00000458013.7	TSL:5 MANE Select	c.40C>A	p.Pro14Thr	missense	Exon 1 of 12	ENSP00000400333.2	Q96L92-1
SNX27	ENST00000368843.8	TSL:1	c.40C>A	p.Pro14Thr	missense	Exon 1 of 12	ENSP00000357836.3	Q96L92-3
SNX27	ENST00000368841.7	TSL:1	n.40C>A		non_coding_transcript_exon	Exon 1 of 12	ENSP00000357834.2	H7C603

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

40472

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1278372

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

625666

African (AFR)

AF:

0.00

AC:

AN:

25736

American (AMR)

AF:

0.00

AC:

AN:

16664

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19056

East Asian (EAS)

AF:

0.00

AC:

AN:

28334

South Asian (SAS)

AF:

0.00

AC:

AN:

63172

European-Finnish (FIN)

AF:

0.00

AC:

AN:

41034

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5072

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1026648

Other (OTH)

AF:

0.00

AC:

AN:

52656

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152188

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41452

American (AMR)

AF:

0.00

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000119

AC:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Severe myoclonic epilepsy in infancy (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.058

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.41

LIST_S2

Benign

0.78

M_CAP

Pathogenic

0.45

MetaRNN

Benign

0.0071

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

0.82

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-0.43

REVEL

Benign

0.045

Sift

Benign

0.043

Sift4G

Benign

0.75

Polyphen

0.012

Vest4

0.13

MutPred

0.22

Gain of phosphorylation at P14 (P = 0.0207)

MVP

0.093

MPC

0.66

ClinPred

0.48

GERP RS

1.0

PromoterAI

0.16

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.11

gMVP

0.54

Mutation Taster

=87/13

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over